The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1411392
This article is part of the Research Topic New Frontiers in Immune Tolerance in Hematopoietic Stem Cell Transplantation View all 7 articles
Galectin-1 is associated with hematopoietic cell engraftment in murine MHC-mismatched allotransplantation
Provisionally accepted- 1 Department of Clinical Laboratory Sciences, College of Applied Medical Science, King Khalid University, Abha, Saudi Arabia
- 2 Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States
- 3 Department of Biology, The Catholic University of America, Washington, D.C., District of Columbia, United States
- 4 Miltenyi Biotec (USA), Gaithersburg, Maryland, United States
- 5 Flow Cytometry Core, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, Maryland, United States
Abstract Haploidentical hematopoietic cell transplantation (haplo-HCT) is associated with an increased risk of allograft rejection. Here, we employed a major histocompatibility complex (MHC)-mismatched allogeneic HCT (allo-HCT) murine model to better understand the role of Gal-1 in immune tolerance. Transplanted mice were classified into either rejected or engrafted based on donor chimerism levels. We noted significantly higher frequencies of CD4+ T cells, CD8+ T cells, natural killer cells, IFN- and TNF-producing CD4+ T cells, and IFN-γ producing dendritic cells and macrophages in rejected mice. Conversely, we found significantly increased frequencies of regulatory T cells (Tregs), predominantly Helios+, IL-10-producing CD4+ T cells, type 1 regulatory (Tr1) cells, and the proportion of Tr1+Gal-1+ cells in engrafted mice. Further, Gal-1 specific blockade in Tregs reduced suppression of effector T cells in engrafted mice. Lastly, effector T cells from engrafted mice were more prone to undergo apoptosis. Collectively, we have shown that Gal-1 may favor HSC engraftment in an MHC-mismatched murine model. Our results demonstrate that Gal-1-expressing Tregs, especially at earlier time points post-transplant, are associated with inducing immune tolerance and stable mixed chimerism after HCT.
Keywords: Galectin-1, tolerance, Haplo-HCT, Tregs, chimerism * Correspondence
Received: 02 Apr 2024; Accepted: 26 Aug 2024.
Copyright: © 2024 Shaikh, Gangaplara, Ali, Xu, Kabore, Kone, Almengo, Saxena, Lopez-Ocasio, McCoy and Fitzhugh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Courtney D. Fitzhugh, Cellular and Molecular Therapeutics Branch, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, 9000, Maryland, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.